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Biomedical subjects

K Wang

Publications and source records attributed to K Wang.

At least 91 records · Page 5Linked to original sources
PubMed2001

Prevention of autoimmune myocarditis through the induction of antigen-specific peripheral immune tolerance.

BACKGROUND: Autoimmunity to cardiac antigens, in particular cardiac myosin, has been observed in humans with myocarditis and in animals with experimental inflammatory heart disease. Current treatments for myocarditis are in many cases immunosuppressive and might lead to increased cardiac damage by reducing host defenses against infectious agents. Therefore, we sought to develop an antigen-specific approach to inhibit autoimmunity in mice with myosin-induced experimental autoimmune myocarditis. METHODS AND RESULTS: Syngeneic splenocytes, coupled with cardiac myosin by use of ethylene carbodiimide, were administered intravenously before disease induction, and the effects of this peripheral tolerization on myosin-induced myocarditis were assessed. This antigen-specific immunotherapy significantly reduced both the incidence and severity of myocarditis, with the prevention of myocyte necrosis, mononuclear cell infiltration, and fibrosis. Myosin-specific delayed-type hypersensitivity and antibody production were significantly reduced, demonstrating that peripheral tolerance affected both T- and B-cell responsiveness to the autoantigen. CONCLUSIONS: These results suggest that the induction of antigen-specific peripheral immune tolerance may be an effective approach for the treatment of myocarditides with autoimmune involvement.

Animals↗
PubMed2001

Homozygosity mapping places the acrodermatitis enteropathica gene on chromosomal region 8q24.3.

Acrodermatitis enteropathica (AE) is a rare autosomal recessive pediatric disease characterized by dermatitis, diarrhea, alopecia, and growth failure. The disease results from insufficient uptake of zinc by the intestine and can be fatal unless the diet is supplemented with zinc. To map the gene responsible for AE, a genomewide screen was performed on 17 individuals, including 4 affected individuals, in a consanguineous Jordanian family. Three markers-D8S373, D10S212, and D6S1021-had a pattern consistent with tight linkage to a recessive disease: one allele in the affected sibs and multiple alleles in unaffected sibs and parents. Two-point parametric linkage analysis using FASTLINK identified one region, D8S373, with a maximum LOD score >1.5 (1.94 at D8S373: recombination fraction.001). Twelve additional markers flanking D8S373 were used to genotype the extended family, to fine-map the AE gene. All five affected individuals-including one who was not genotyped in the genomewide screen-were found to be homozygous for a common haplotype, spanning approximately 3.5 cM, defined by markers D8S1713 and D8S2334 on chromosomal region 8q24.3. To support these mapping data, seven consanguineous Egyptian families with eight patients with AE were genotyped using these markers, and six patients from five families were found to be homozygous in this region. Multipoint analysis with all consanguineous families, by Mapmaker/Homoz, resulted in a maximum LOD score of 3.89 between D8S1713 and D8S373. Sliding three-point analysis resulted in a maximum LOD score of 5.16 between markers D8S1727 and D8S1744.

Acrodermatitis↗
PubMed2001

Lanthanide ions induce hydrolysis of hemoglobin-bound 2,3-diphosphoglycerate (2,3-DPG), conformational changes of globin and bidirectional changes of 2,3-DPG-hemoglobin's oxygen affinity.

The changes in structure and function of 2,3-diphosphoglycerate-hemoglobin (2,3-DPG-Hb) induced by Ln(3+) binding were studied by spectroscopic methods. The binding of lanthanide cations to 2,3-DPG is prior to that to Hb. Ln(3+) binding causes the hydrolysis of either one from the two phosphomonoester bonds in 2,3-DPG non-specifically. The results using the ultrafiltration method indicate that Ln(3+) binding sites for Hb can be classified into three categories: i.e. positive cooperative sites (N(I)), non-cooperative strong sites (N(S)) and non-cooperative weak sites (N(W)) with binding constants in decreasing order: K(I)>K(S)>K(W). The total number of binding sites amounts to about 65 per Hb tetramer. Information on reaction kinetics was obtained from the change of intrinsic fluorescence in Hb monitored by stopped-flow fluorometry. Fluctuation of fluorescence dependent on Ln(3+) concentration and temperature was observed and can be attributed to the successive conformational changes induced by Ln(3+) binding. The results also reveal the bidirectional changes of the oxygen affinity of Hb in the dependence on Ln(3+) concentration. At the range of [Ln(3+)]/[Hb]<2, the marked increase of oxygen affinity (P(50) decrease) with the Ln(3+) concentration can be attributed to the hydrolysis of 2,3-DPG, while the slight rebound of oxygen affinity in higher Ln(3+) concentration can be interpreted by the transition to the T-state of the Hb tetramer induced by Ln(3+) binding. This was indicated by the changes in secondary structure characterized by the decrease of alpha-helix content.

2,3-Diphosphoglycerate↗
PubMed2001

Equilibrium and kinetics studies of transnitrosation between S-nitrosothiols and thiols.

Using UV-vis spectrometrical measurements, equilibrium constants for NO transfer between S-nitroso-N-acetyl-penicillamine (SNAP) and different thiols as well as kinetic data for NO transfer from S-nitroso bovine serum albumin (BSANO) to thiols have been obtained. NO transfer from SNAP to other primary/secondary thiols are thermodynamically favorable, whereas other S-nitrosothiols exhibit similar NO transfer potential. The obtained Gibbs free energy, enthalpy and entropy data indicated that NO transfer reactions from SNAP to four thiols are exothermic with entropy loss. The kinetic behavior of BSANO/RSH transfer can be related to both the acidity of sulfhydryl group and the electronic structure in thiol.

Kinetics↗
PubMed2001

High-affinity actin-binding nebulin fragments influence the actoS1 complex.

Human nebulin fragments, NA3 and NA4, corresponding to individual superrepeats display high-affinity interactions with individual actin protomers in cosedimentation and solid-phase binding assays. Stoichiometric analysis of nebulin fragment-induced actin polymerization and inhibition of actin-activated S1 ATPase indicate that one superrepeat influences multiple actin molecules along the F-actin filament, consistent with a combination of strong and weak interactions of nebulin over the length of the actin filament. The mechanisms by which human nebulin fragments affect the interaction between actin and myosin S1 are studied by fluorescence quenching, polarization, and resonance energy transfer. We show that, under strong binding conditions, premixing actin with the NA3 prior to adding myosin subfragment 1 (S1) inhibits the rate of actoS1 association. The nebulin fragments, NA3 and NA4, caused little effect on the extent of actoS1 binding at equilibrium but did alter the nature of the complex as evidenced by an increase in the resonance energy transfer efficiencies between S1 and actin in the absence of ATP. The addition of low concentrations of ATP rapidly dissociates the strong-binding actoS1 irrespective of the presence or absence of nebulin fragment. Interestingly, the strongly bound state reforms rapidly after S1 hydrolyzes all available ATP. These observations are consistent with the notion that nebulin might contribute to optimizing the alignment of actomyosin interactions and inhibit suboptimal actomyosin contacts.

Actins↗
PubMed2001

Transplantation of infantile bladder in rats: an alternative procedure for bladder augmentation.

BACKGROUND: Our purpose was to evaluate whether bladder transplantation (BTx) can be used for bladder augmentation (BA). METHODS: Bladders from infantile Brown-Norway rats (less than 21 days old) were excised and each transplanted into a pouch created in the distal omentum of a 6-week-old Lewis rat (fully allogeneic BTx). No immunosuppressant was used in group I (n=12). Intramuscular FK506 was used daily from the day of BTx in group II (n=16; 0.2 mg/kg), group III (n=22; 0.6 mg/kg), and group IV (n=16; 1.2 mg/kg) until harvesting 3, 4, 5, or 6 weeks after BTx. FK506 was used for only 2 weeks in group V (n=12; 0.6 mg/kg/day) and group VI (n=12; 1.2 mg/kg/day). Syngeneic bladder transplants acted as controls (n=16). Hematoxylin and eosin staining was used to examine all grafts. In six rats from group III, BA was performed by anastomosing the graft to the recipient bladder 10 days after BTx. RESULTS: Each successfully transplanted graft appeared macroscopically as a thin-walled cyst. Rejection was seen in all grafts from groups I, II, V, and VI, and was minimal or absent in groups III and IV. On medium to long-term follow-up the only side effect of FK506 observed was reduced weight gain. Graft survival in the control group was 100%. BA was successful in all six cases, and the mucosa was normal throughout each augmented bladder. CONCLUSIONS: This is the first report of the successful transplantation of infantile tissue without vascular anastomosis. Because of the efficient, safe immunosuppression possible with FK506, our BTx technique could find clinical application for creating viable vesical tissue that could be used for BA.

Animals↗
PubMed2001

Toward separation and purification of olefins using dithiolene complexes: an electrochemical approach.

The complex Ni[S2C2(CF3)2]2 reacts with light olefins, including ethylene and propylene, selectively and reversibly. The reaction is not poisoned by hydrogen gas, carbon monoxide, acetylene, or hydrogen sulfide, which are commonly present in olefin streams, presumably because olefin binding occurs through the sulfur ligand rather than the metal center. The reversible reaction of olefins with Ni[S2C2(CN)2]2n (n = 0, -1, -2) can be controlled electrochemically, where the oxidation state-dependent binding and release of olefins are fast on the electrochemical time scale. The observed tolerance to poisons and controllable electrochemical reactivity present an alternative approach to the separation of olefins from complex streams.

Journal Article↗
PubMed2001

Combined multipoint analysis of multiple asthma data sets based on the posterior probability of linkage.

In the presence of multiple data sets, an important issue is how to best measure the overall evidence for linkage across data sets. Previously, we advocated the use of the posterior probability of linkage (PPL) for this purpose [Vieland, Am J Hum Genet 63:947-54, 1998; Wang et al., Ann Hum Genet 64:533-53, 2000; Vieland et al., Hum Hered 51:199-208, 2001]. In this paper, we propose a critical modification of our earlier two-point PPL in order to handle multiple-point calculations. The proposed modification is then applied to the genome-screen data sets and the COAG chromosome 5 data sets provided by GAW 12. We find linkage signals at location (in the order of the strength of the signal) 45 cM on chromosome 6, 23 cM on chromosome 20, and 30 cM on chromosome 1. No linkage signal is found on chromosome 5.

Adult↗
PubMed2001

Intravascular low-power laser irradiation after coronary stenting: long-term follow-up.

BACKGROUND AND OBJECTIVE: A high restenosis rate remains a limiting factor for percutaneous transluminal coronary angioplasty and stenting. The objective of this study was to evaluate the effect of intravascular red laser therapy (IRLT) on restenosis after stenting procedures in de novo lesions. STUDY DESIGN/MATERIALS AND METHODS: A total of 68 consecutive patients were treated with IRLT in conjunction with coronary stenting procedures. Mean lesion length was 16.5 +/- 2.4 mm. Reference vessel diameter (RVD) and pre-minimal lumen diameter (MLD) were 2.90 +/- 0.15 mm and 1.12 +/- 0.26 mm, respectively. RESULTS: After treatment, MLD was 2.76 +/- 0.32 mm with no procedural complications or in-hospital adverse events. Angiographic follow-up (n = 61) revealed restenosis in nine patients (14.7%) with rate by artery size of > 3 mm (n = 21) 0%; 2.5--3.0 mm (n = 28) 14.2%; and < 2.5 mm (n = 12) 41.6%. CONCLUSION: Intravascular red light therapy is safe, feasible, and reduces expected restenosis rate after coronary stenting.

Aged↗
PubMed2001

Production of an anti-prostate-specific antigen single-chain antibody fragment from Pichia pastoris.

Prostate-specific antigen (PSA) is a widely used marker for screening and monitoring prostate cancer. Because PSA levels are normally quite low, an antibody-based assay must be used to detect PSA. However, not all PSA-specific antibodies bind equally well to PSA or to its different isoforms. Therefore, a better understanding of how PSA interacts with PSA-specific antibodies is of considerable clinical interest. B80.3 is a widely used murine monoclonal anti-PSA antibody (IgG), which has very high affinity for both free and alpha-anti-chymotrypsin complexed PSA. More importantly, its gene sequence is known-making it one of only two anti-PSA antibodies that has been fully cloned and sequenced. To better elucidate the interaction between PSA and B80.3, a single-chain antibody fragment, derived from the variable domain of B80.3 (scFvB80), was cloned into a pPIC9 vector and expressed in Pichia pastoris. The secreted protein was purified using a three-step protocol beginning with a 50% ammonium sulfate precipitation step, followed by a T-gel thio-affinity step and concluding with a simple anion-exchange (DE52) filtration step. NMR studies indicate the protein is correctly folded while competitive enzyme-linked immunosorbant assays show that the purified scFvB80 has approximately 20% of the activity of the full-length B80.3 antibody. The protocol described here provides a quick and convenient route to prepare large quantities of very pure anti-PSA antibody fragments (15-20 mg/L culture medium) for detailed structural and biophysical characterization.

Animals↗
PubMed2001

Effects of local and remote muscle pain on human jaw reflexes evoked by fast stretches at different clenching levels.

Muscle pain imposes significant changes on natural motor tasks, but the consequences for stretch reflexes are still disputed. The present study examined the jaw reflexes to fast (10 ms) stretches of the mandible in an experimental model with local pain in the masseter muscle and remote pain in the tibialis anterior muscle. The stretch reflexes were elicited in healthy volunteers (n=13) before, during, and after periods with constant levels of experimental pain and while the subjects clenched at 0%, 15%, 30%, and 45% of the maximal voluntary contraction (MVC) levels. Surface electromyography (EMG) was used to record the reflex responses. Pain in the masseter muscle (mean +/- SEM, 3.8+/-0.4 on a 10-cm visual analogue scale), but not in the tibialis anterior muscle (3.4+/-0.3; paired t-test, P=0.318) was associated with significant changes in both prestimulus EMG activity (ANOVA, P=0.002) and in peak-to-peak amplitudes of the stretch reflex (ANOVA, P=0.022). However, when the changes in prestimulus EMG activity were taken into consideration a significant increase in the stretch reflex persisted in the painful muscle at 15% and 30% MVC. Local circuits at the trigeminal level involving the fusimotor system are proposed to mediate a significant part of this modulatory effect.

Adult↗
PubMed2001

Characterization of the Japanese pufferfish (Takifugu rubripes) T-cell receptor alpha locus reveals a unique genomic organization.

Polymerase chain reactions with degenerate V gene segment primers were used to isolate the putative T-cell receptor alpha-chain gene (TCRA) from Japanese pufferfish (Takifugu rubripes). The putative TCRA chain cDNA is composed of an N-terminus leader peptide followed by the variable region and the constant region. The variable portion of the TCRA gene is encoded by V and J gene segments separated in the germline. As in mammals, the V-J junction sequences are GC rich and highly diversified. Amino acid residues that are required to maintain the function and structural integrity of the TCRA polypeptide, including the conserved Trp-Tyr-Lys and Tyr-Tyr-Cys motifs in the V gene segments, the Lys-Leu-X-Phe-Gly-X-Gly-Thr-X-Leu motif in the J gene segment, the three cysteine residues in the constant region and the charged residues in the transmembrane region are all preserved in the pufferfish. These conserved features suggest that the TCRA gene families in fish and mammals have evolved from a common ancestor.

Amino Acid Sequence↗
PubMed2001

Excitatory actions of experimental muscle pain on early and late components of human jaw stretch reflexes.

It has recently been shown that a slow stretch evokes a short-latency (probably monosynaptic) and a long-latency (polysynaptic) reflex response in human jaw-closing muscles. The effect of nociceptive muscle input on the fusimotor system has not been investigated in detail. In order to investigate the effect of sustained muscle pain on the jaw stretch reflex, two main experiments were performed. Stretch reflex responses were evoked in the masseter and temporalis muscles by slow stretches (1-mm displacement, 40-ms ramp time) before, during and 15 min after a period of experimentally induced muscle pain. In experiment I, a dose of 1.0 M hypertonic or 154 mM isotonic (control) saline was infused in random order into the left masseter for up to 15 min (n=12). The level of excitation of the left masseter at 15% maximal voluntary contraction was controlled by visual feedback of the surface EMG (sEMG). In experiment II, a dose of 1.0 M saline was infused into the left masseter but with feedback from the sEMG of the right masseter (n=12). In a control experiment, both sEMG and intramuscular EMG (imEMG) were recorded from the left and right masseters; the feedback was from imEMG of the left masseter (n=12). The early (onset: 9--10 ms) and late (duration from 25 to 40 ms) reflex components were recorded and analysed in all experiments. Infusion of 1.0 M saline caused moderate pain (mean score on a Visual Analogue Pain Scale: 4.9--5.0 cm). The peak-to-peak amplitude of the early reflex component in the painful masseter normalized to the pre-stimulus EMG activity was significantly higher during the pain than the pre- and post-infusion conditions in all experiments. The normalized area of the late reflex component in the painful masseter was significantly larger than in the pre-infusion condition in all experiments. Isotonic saline had no significant effect on the jaw stretch reflexes. These results indicate that experimental jaw-muscle pain in humans facilitates the early as well as the late component of the jaw stretch reflex response as revealed by both sEMG and imEMG. This effect appears to be independent of the level of excitation of the muscle and not related to volume effects of the injected saline. A change in the sensitivity of the fusimotor system during muscle pain is suggested as an explanation.

Adult↗
PubMed2001

Flow field and oscillatory shear stress in a tuning-fork-shaped model of the average human carotid bifurcation.

The oscillatory shear index (OSI) was developed based on the hypothesis that intimal hyperplasia was correlated with oscillatory shear stresses. However, the validity of the OSI was in question since the correlation between intimal thickness and the OSI at the side walls of the sinus in the Y-shaped model of the average human carotid bifurcation (Y-AHCB) was weak. The objectives of this paper are to examine whether the reason for the weak correlation lies in the deviation in geometry of Y-AHCB from real human carotid bifurcation, and whether this correlation is clearly improved in the tuning-fork-shaped model of the average human carotid bifurcation (TF-AHCB). The geometry of the TF-AHCB model was based on observation and statistical analysis of specimens from 74 cadavers. The flow fields in both models were studied and compared by using flow visualization methods under steady flow conditions and by using laser Doppler anemometer (LDA) under pulsatile flow conditions. The TF-shaped geometry leads to a more complex flow field than the Y-shaped geometry. This added complexity includes strengthened helical movements in the sinus, new flow separation zone, and directional changes in the secondary flow patterns. The results show that the OSI-values at the side walls of the sinus in the TF-shaped model were more than two times as large as those in the Y-shaped model. This study confirmed the stronger correlation between the OSI and intimal thickness in the tuning-fork geometry of human carotid bifurcation, and the TF-AHCB model is a significant improvement over the traditional Y-shaped model.

Adult↗
PubMed2001

What happens to the bladder at night? Overnight urodynamic monitoring in children with neurogenic vesical dysfunction.

PURPOSE: We assess night and day function of the neuropathic bladder in children with neurogenic vesical dysfunction by overnight urodynamic monitoring and conventional static cystometrogram. Overnight urodynamics as a diagnostic tool was evaluated and its reproducibility analyzed. MATERIALS AND METHODS: In 18 months 3 boys and 3 girls 6 to 14 years old (mean age plus or minus standard deviation 10.3 +/- 3.3) were studied prospectively. Each child was evaluated on 4 separate occasions with 2-daytime cystometrograms at a standard fill rate of 10 ml. per minute and 2 overnight urodynamic studies for 8 hours using a Urolog Recorder. All 6 children were interviewed regarding the acceptability, repeatability and compliance to overnight urodynamics. RESULTS: Bladder capacity was not significantly different during each episode for either of the 2 tests. Mean bladder pressures in 2 children showed stable detrusor activity on cystometry (2 +/- 1.4 cm. H2O) and overnight urodynamics (0.4 +/- 0.5, r = 0.9). Detrusor compliance was not impaired in these 2 children. Four patients had frank detrusor instability with a mean bladder pressure of 50.6 +/- 17.4 cm. H2O on cystometry versus 35.9 +/- 5.2 on overnight urodynamics (r = 0.9). Bladder compliance was severely impaired in these 4 patients. Compliance at potential bladder capacity for patient age was 6.6 +/- 2.1 ml./cm. H2O for cystometry versus 9.2 +/- 3.4 for overnight urodynamics (p = 0.26, r = 0.9). Compliance at actual bladder capacity was 3.4 +/- 1.2 ml./cm. H2O for cystometry versus 3.8 +/- 0.8 for overnight urodynamics (p = 0.28, r = 0.9). There was good correlation between daytime cystometry and overnight urodynamics (p <0.001, Pearson's coefficient correlation 0.92, 95% confidence interval 0.90 to 0.94). A kappa statistical analysis showed good agreement between cystometry and overnight urodynamics for stable bladder and frank detrusor instability (kappa = 0.9). Replicated measurements of the same patient by the same observer had an error of variance of 1.7 cm. H2O with a narrow confidence interval, indicating the measurement error was small and that overnight urodynamics can be reproduced with relative accuracy within an individual. All 6 children preferred overnight urodynamics to cystometry. CONCLUSIONS: There was good correlation between bladder behavior day and night. Overnight urodynamics were accurate in predicting detrusor activity, and well tolerated and less embarrassing for a child with neurogenic vesical dysfunction.

Adolescent↗
PubMed2001

Global stability of an SEIS epidemic model with recruitment and a varying total population size.

This paper considers an SEIS epidemic model that incorporates constant recruitment, disease-caused death and disease latency. The incidence term is of the bilinear mass-action form. It is shown that the global dynamics is completely determined by the basic reproduction number R(0). If R(0) 1, a unique endemic equilibrium is globally stable in the interior of the feasible region and the disease persists at the endemic equilibrium.

Communicable Diseases↗
PubMed2001

Use of precision agriculture technology to investigate spatial variability in nitrogen yields in cut grassland.

Spatial variability in N uptake and utilisation by swards within uniformly managed field units could be responsible for a significant proportion of the NH3, N2O, NO3- and NOx (NO and NO2) 'pollutants' generated by agriculture and released to the environment. An investigation was commenced, therefore, to quantify, map and explain the spatial variability in sward N yield in a 'large' silage field and to assess the potential for managing this variability using some of the latest precision agriculture technology. Sward dry matter (DM) and N yields were predicted from the results of plant tissue analyses using mathematical models. Sward N yields were found to vary greatly across the field seemingly because of differences in net soil N mineralisation, but the pattern of variability appeared to remain constant with time. Conventional soil analysis of a range of soil chemical and physical properties, however, failed to explain this variability. It was concluded that the N-yield distribution map might be used in place of soil analysis as the basis for varying the rates of N application to different parts of the field with the twin objectives of maximising fertiliser use efficiency and minimising N emissions to air and water.

Agriculture↗